Luis Aragon及其同事发现,被连接到DNA损伤点上的“黏连蛋白”是被“分离酶”分离的,“黏连蛋白”的分离是发生切除所必需的。本文作者猜测,如果“黏连蛋白”的分离在哺乳动物模型中得到保留的话,那么依靠DND病灶治疗方法就有可能通过同时抑制“黏连蛋白”环得到改进。

-2013年1月10日版《自然》

中文翻译


【译文】“黏连蛋白”环的分离是DNA修复的构成部分

【译文】DNA双链断裂修复对于细胞生存至关重要,并且涉及高度协同的通路以修复在损伤部位的DNA完整性。同源依赖的修复期间早期事件即为断裂的消除以逐渐产生更长的3’单链尾部,这些尾部被用于鉴定修复的合适模板。姐妹染色单体提供了近似完美的序列同源性,因此成为同源重组首选模板。为了提供利用姐妹染色单体作为供体的基础,聚合物(将姐妹染色单体联系一起)被招募至断裂处以增强相似性。本研究表明DNA断裂促进芽殖酵母S期前期时聚合物的分离,而聚合物损伤诱导的解离需要分离酶,这种分离酶是在分裂后期分解聚合物的蛋白酶。此外,编码聚合物α-kleisin亚基Mcd1 (又称Scc1)基因的分离酶耐受等位基因减少了双链断裂反应,甚至在DNA损伤期降低修复效能,我们得到如下结论,即复制后DNA修复涉及依赖分离酶的聚合物分裂,促进修复协同的细胞反应存储DNA完整性因子的可能性。

英文原稿


[Title]: Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesion

[Authors]:Alexandra McAleenan,1, 2 Andres Clemente-Blanco,1, 2 Violeta Cordon-Preciado,1 Nicholas Sen,1 Miguel Esteras,1 Adam Jarmuz1 & Luis Aragón1

[Abstract]DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively longer 3′ single-strand tails that are used to identify suitable templates for repair. Sister chromatids provide near-perfect sequence homology and are therefore the preferred templates during homologous recombination. To provide a bias for the use of sisters as donors, cohesin—the complex that tethers sister chromatids together—is recruited to the break to enforce physical proximity. Here we show that DNA breaks promote dissociation of cohesin loaded during the previous S phase in budding yeast, and that damage-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anaphase. Moreover, a separase-resistant allele of the gene coding for the α-kleisin subunit of cohesin, Mcd1 (also known as Scc1), reduces double-strand break resection and compromises the efficiency of repair even when loaded during DNA damage. We conclude that post-replicative DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors during the coordinated cellular response to restore DNA integrity.

原文地址

http://www.nature.com/nature/journal/v493/n7431/full/nature11630.html

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